Search Results

You are looking at 1 - 3 of 3 items for

  • Author or Editor: Toshihiko Ando x
  • All content x
Clear All Modify Search
Restricted access

Katsunobu Takenaka, Hiromu Yamada, Noboru Sakai, Takashi Ando, Toshihiko Nakashima, and Yasuaki Nishimura

✓ The purpose of this study was to determine the effects of cerebrospinal fluid (CSF) from patients with subarachnoid hemorrhage (SAH) on cytosolic free calcium in cultured rat vascular smooth-muscle cells using the fluorescent intracellular calcium indicator fura-2/AM. Samples of CSF were collected from 12 patients (seven with and five without vasospasm) on Days 2, 6, 11, and 16 after SAH. Control CSF samples were obtained from five patients 6 to 9 months after they had undergone successful aneurysm surgery following an SAH. All CSF samples in both the non-vasospasm and vasospasm groups, regardless of the day of sampling after the SAH, induced significantly higher transient intracellular calcium elevations when compared to levels induced by control CSF. Furthermore, the addition of 2 mM ethyleneglycol-bis (β-aminoethylether)-N,N'-tetra-acetic acid (EGTA) caused a slight reduction in the peak height in the CSF-induced intracellular calcium rise which declined more rapidly to basal levels than those studied without EGTA. In the non-vasospasm group, the intracellular calcium concentration remained stable after SAH throughout the study period. In contrast, in the vasospasm group, this concentration was highest on Day 2 post-SAH, but sharply decreased on Day 6 and rose again on Day 11. This result correlated with the clinical signs of vasospasm in these patients. These findings indicated that the intracellular calcium elevations induced by CSF obtained after SAH were due to the combination of the influx of extracellular calcium and the mobilization of intracellular calcium from storage sites. The changes in intracellular calcium concentrations in vascular smooth-muscle cells induced by CSF obtained from patients on successive days following SAH suggest that the substances that induce this repeat calcium elevation on Day 11 post-SAH may be the key spasmogens for vasospasm after SAH.

Restricted access

Katsunobu Takenaka, Hiromu Yamada, Noboru Sakai, Takashi Ando, Toshihiko Nakashima, Yasuaki Nishimura, Yukio Okano, and Yoshinori Nozawa

✓ To clarify the mechanism of contractive effects in arteries caused by oxyhemoglobin, changes in the concentration of cytosolic calcium ([Ca++]1) before and after exposure to oxyhemoglobin were measured in vitro in cultured vascular smooth-muscle cells obtained from rat aorta. This was accomplished by preloading these cells with a fluorescent intracellular Ca++ probe fura-2/AM.

Oxyhemoglobin induced a significant elevation of [Ca++]1 in vascular smooth-muscle cells which was sustained for 10 minutes. This response was completely abolished by chelating extracellular calcium with ethyleneglycol-bis (β-aminoethylether)-N,N′-tetra-acetic acid (EGTA). Oxyhemoglobin induced no accumulation of mass content of inositol 1,4,5-trisphosphate (IP3(1,4,5)). The oxyhemoglobin-induced elevation of [Ca++]1 was not blocked by verapamil, a calcium antagonist. Serotonin induced a rapid, transient increase of [Ca++]1 followed by a sustained elevation above baseline for 5 minutes. Additions of EGTA or verapamil had a small effect on the peak height of serotonin-induced [Ca++]1 elevation, but the [Ca++]1 level declined more quickly to the basal level in treated compared with control cells.

These results indicate that oxyhemoglobin-induced [Ca++]1 elevation is caused by the influx of extracellular calcium, which is independent of the verapamil-blocked voltage-gated calcium channel. The long-lasting high elevation of [Ca++]1 caused by oxyhemoglobin suggests that oxyhemoglobin may contribute to the production of abnormal contractions and/or irreversible damage in vascular smooth-muscle cells.

Restricted access

Suguru Igarashi, Toshihiko Ando, Tatsuhiko Takahashi, Jun Yoshida, Masakazu Kobayashi, Kenji Yoshida, Kazunori Terasaki, Shunrou Fujiwara, Yoshitaka Kubo, and Kuniaki Ogasawara


A primary cause of cognitive decline after carotid endarterectomy (CEA) is cerebral injury due to cerebral hyperperfusion. However, the mechanisms of how cerebral hyperperfusion induces cerebral cortex and white matter injury are not known. The presence of cerebral microbleeds (CMBs) on susceptibility-weighted imaging (SWI) is independently associated with a decline in global cognitive function. The purpose of this prospective observational study was to determine whether cerebral hyperperfusion following CEA leads to the development of CMBs and if postoperative cognitive decline is related to these developed CMBs.


During the 27-month study period, patients who underwent CEA for ipsilateral internal carotid artery stenosis (≥ 70%) also underwent SWI and neuropsychological testing before and 2 months after surgery, as well as quantitative brain perfusion SPECT prior to and immediately after surgery.


According to quantitative brain perfusion SPECT and SWI before and after surgery, 12 (16%) and 7 (9%) of 75 patients exhibited postoperative cerebral hyperperfusion and increased CMBs in the cerebral hemisphere ipsilateral to surgery, respectively. Cerebral hyperperfusion was associated with an increase in CMBs after surgery (logistic regression analysis, 95% CI 5.08–31.25, p < 0.0001). According to neuropsychological assessments before and after surgery, 10 patients (13%) showed postoperative cognitive decline. Increased CMBs were associated with cognitive decline after surgery (logistic regression analysis, 95% CI 6.80–66.67, p < 0.0001). Among the patients with cerebral hyperperfusion after surgery, the incidence of postoperative cognitive decline was higher in those with increased CMBs (100%) than in those without (20%; p = 0.0101).


Cerebral hyperperfusion following CEA leads to the development of CMBs, and postoperative cognitive decline is related to these developed CMBs.